DESCRIPTION (Adapted from the applicant's abstract and specific aims): Alveolar macrophage (AM) functions involved in antimicrobial activity, including the respiratory burst (stimulated superoxide production), are altered by exposure to oxidants. The hypothesis is that sublethal oxidative stress alters the respiratory burst through two processes: a) modulation of Ca2+-dependent components of signal transduction by ROOH; and b) formation of adducts to components of signaling and/or the NADPH oxidase by 4-hydroxynonenal (4-HNE). The specific aims are: 1) to determine the mechanism(s) whereby the changes in [Ca2+]i caused by ROOH alter signal transduction for the respiratory burst by measuring the Ca2+-dependent protein kinase C (alpha and beta forms), protein phosphatase 2B, and phospholipase D activities and phosphorylation of p47phox (a component of the respiratory burst oxidase); 2) to determine the source(s) of ROOH-inducible release of [Ca2+]i which differs from the IP3-sensitive pool released during ADP stimulation; and 3) to examine the mechanism(s) of alteration of the respiratory burst by 4-HNE by assessing the potential for direct alteration of NADPH oxidase components or components of signal transduction.